Composite polymer microfluidic control device

ABSTRACT

A device for microfluidic control comprising a regulator that is moveable in a conduit where the regulator is a composite polymer formed from a composite mixture comprising a polymerizable precursor and a particulate filler.

BACKGROUND

Microfluidic systems, that is, systems or devices having channels orchambers that are fabricated on the micron or submicron scale, are usedto perform a multitude of chemical and physical processes on amicro-scale. Individual components of the microfluidic systems can beused alone or together, for example, to control or measure the transportof fluid inside microchannels. Typical applications for microfluidicsystems include analytical and medical instrumentation, industrialprocess control equipment, and liquid and gas phase chromatography. Inthese systems, methods to reliably aliquot volumes of sample from oneconduit into a second conduit are important for performance of theanalysis. In some cases, sample volumes as small as 1 nL are requiredfor analysis, which is a volume too small to be reliably dispensed byknown macroscale methods, such as conventional valves or pipettes. Itwould be advantageous to have a microfluidic system that could be usedwith a wide range of processes and process liquids and could befabricated on a microchip platform. It would also be advantageous tohave a device with a fast response time and precise control over smallsample volumes and flows.

Microfluidic control devices, such as microvalves manufactured fromsilicon or elastomers, including devices fabricated from hydrogels, softelastomers with control lines embossed in a substrate, and devicesfabricated with structures that are free to move within microchannelsare currently known. More information on these devices can be found inShoji and Esashi, J., Micromech. Microeng., 4, 157-171, 1994; Beebe etal., Nature, 404, 588-590, April 2000; Unger et al., Science, 288,113-116, April 2000; and Rehm et al., uTAS 2001, 227-229, October 2001.Disadvantageously, however, these devices suffer from one or more of thedisadvantages of not being easily integrated into microchip platforms,have excess dead volume, high power requirements, slow response times,are difficult and costly to manufacture and assemble, are able towithstand only modest pressure differentials, are restricted to a narrowrange of processes and process liquids, are subject to solvent-induceddeformation effects, exhibit performance variations from minorvariations in material properties, and respond poorly to solvent-inducedshrinkage and swelling.

Therefore, there is a need for a microfluidic control device that has afast response time, precise control over small gas and liquid flows, andprecise control over small gas and liquid volumes in the channels andchambers of microfluidic systems. There is also a need for amicrofluidic control device that can be integrated into a microchipplatform and is compatible with a wide range of chemical solvents thatare used in microfluidic systems.

SUMMARY

According to the present invention, a device for microfluidic control isprovided. The device comprises a conduit having a first end and a secondend, a first path in fluid flow contact with the conduit, a second pathin fluid flow contact with the conduit, and a regulator that is moveablein the conduit. The regulator has an outer dimension that is larger thanthe first end and the second end so the regulator cannot pass out of theconduit and is comprised of a substantially elastic material having astructural component, which can be a composite polymer formed from acomposite mixture comprising a polymerizable precursor and a particulatefiller. The composite mixture can additionally comprise aphoto-initiator, and/or two or more polymerizable precursors.Optionally, the device can have a plurality of paths, such as first,second, and third paths, where each path is in fluid flow contact withthe conduit, and/or a plurality of regulators that are movable in aconduit. The regulator can be substantially incompressible, have opticalproperties, and/or have a substantially stable volume when exposed to afluid. Further, the regulator can be formed from a composite mixture inthe conduit by the in situ polymerization of the composite mixture withan energy source. The composite mixture can additionally comprise aphoto-initiator and the energy source can be a radiating light source.The regulator can also be substantially cylindrically shaped andmoveable in a back and forth motion or reciprocating motion within theconduit. Alternately, the regulator can be substantially toothed wheelshaped and rotationally moveable within the conduit. The device canadditionally comprise a substrate where the conduit, and/or a pluralityof conduits are in the substrate. Optionally, the substrate can have anaxle and the regulator can be substantially toothed wheel shaped androtationally moveable around the axle.

A system for microfluidic control comprising a plurality of conduits isalso provided, where each conduit has a first end and a second end, afirst path in fluid flow contact with one or more conduit, a second pathin fluid flow contact with one or more conduit, and a plurality ofregulators, each regulator being independently moveable in a separateconduit. Each regulator has an outer diameter that is larger than thefirst end and the second end so each regulator cannot pass out of theconduit, and is comprised of a substantially elastic material having astructural component.

The device can be fabricated by combining a polymerizable precursor anda particulate filler to form a composite mixture, introducing thecomposite mixture into a conduit, and exposing the conduit to an energysource to polymerize the composite mixture in situ thereby forming aregulator. The composite mixture can additionally comprise aphoto-initiator and the conduit can be exposed to a radiating lightsource through a mask to form the regulator. Additionally, the devicecan have two or more regulators within each conduit, and/orunpolymerized composite mixture can be removed from the conduit.Optionally, a substrate having a plurality of conduits can be selectedand the composite mixture can be introduced into each conduit, therebyforming a plurality of regulators. The substrate can have three or moreconduits and the composite mixture can be introduced into three or moreconduits to form three or more regulators on the same substrate. One ormore of the conduits can be exposed to a radiating light to form one ormore substantially cylindrically shaped regulators and eachsubstantially cylindrically shaped regulator can be moveable in a backand forth motion within the conduit. Alternately, one or more of theconduits can be exposed to a radiating light to form one or moresubstantially toothed wheel shaped regulators and each substantiallytoothed wheel shaped regulator can be rotationally moveable within theconduit. The substrate can additionally have an axle and the conduit canbe exposed to a radiating light to form a substantially toothed wheelshaped regulator around the axle.

The device can be used for determining a fluid flow rate in amicrofluidic device by moving a fluid with a viscosity past a regulator,thereby moving the regulator at the fluid flow rate. A radiating lightis directed to a portion of the regulator such that the radiating lightis reflected or transmitted to a detector and the reflected ortransmitted light is measured as a periodic signal in time. Then, thesignal is processed and the frequency of the signal is determined,followed by relating the signal frequency to the fluid flow rate. Theradiating light can be reflected or transmitted to a plurality ofdetectors. Also, a plurality of radiating lights can be directed to theregulator and the radiating lights can be reflected or transmitted to aplurality of detectors. A device for microfluidic control as describedabove having a substantially toothed wheel shaped regulator can be usedto determine fluid flow rate and the radiating light can be directed toa toothed portion of the regulator such that the radiating light isreflected or transmitted to the detector.

DRAWINGS

These and other features, aspects and advantages of the presentinvention will become better understood from the following description,appended claims, and accompanying drawings where:

FIG. 1A, 1B and 1C schematically show a microfluidic control devicewhere the device is a composite check valve according to the presentinvention;

FIG. 2A, 2B, 2C, and 2D schematically show a microfluidic control devicewhere the device is a composite check valve with an integrated flow pathaccording to the present invention;

FIG. 3A and 3B schematically show a system comprising a plurality ofmicrofluidic control devices where the system is a used as a fluiddispenser according to the present invention;

FIG. 4A and 4B schematically show a microfluidic control device wherethe device is a mixing valve according to the present invention;

FIG. 5A and 5B schematically show a microfluidic control device wherethe device is a flow meter comprising a substantially toothed wheelshaped regulator that is rotationally moveable within a conduitaccording to the present invention;

FIG. 6 schematically shows a microfluidic control device where thedevice comprises a plurality of gears used to perform mechanical workaccording the present invention;

FIG. 7 schematically shows a method of making a device for microfluidiccontrol according to the seventh embodiment of the present invention;and

FIG. 8 is a flow chart showing a method of using a device formicrofluidic control for determining a fluid flow rate according to thepresent invention.

DESCRIPTION

According to one embodiment of the present invention, there is provideda device for microfluidic control. The device comprises a regulator thatis moveable in a conduit and is formed from a composite mixturecomprising a polymerizable precursor and a particulate filler. The useof a particulate filler in the regulator confers a wide range ofdesirable properties to the regulator, such as, a range of rigidityversus flexibility, additional tensile and compressive strength, opticalproperties, and dimensional stability. The regulator can operate underhigh pressure, such as thousands of pounds per square inch (psi), andthe addition of the particulate filler to the regulator providessubstantial advantages in reduced compressibility. Further, themicrofluidic control device of the present invention has a fast responsetime and precise control over small gas and liquid flows and small gasand liquid volumes in the channels and chambers of the microfluidicsystem. Further, the microfluidic control device can be integrated intoa substrate, such as a microchip platform.

The microfluidic control device of the present invention can includeinterconnecting conduits that can be filled with fluids. These devicescan be used for analytical procedures such as analysis of chemical andbiological substances. Examples of such devices include high-performanceliquid chromatography (HPLC) and flow-injection analysis (FIA).

As used in this disclosure, the following terms have the specifiedmeanings.

The term “composite polymer” means a material obtained by thepolymerization of a mixture of a particulate filler and one or morepolymerizable precursors.

The term “conduit” means any of various channels or networks of channelsincluding capillaries and tubing.

The term “elastic material” means a material that recovers its originalshape partially or completely after a deforming force has been removed.

The term “fluid” means any of various liquids, gasses, or loose solidmaterials in bulk.

The term “micro-scale” means a micron or submicron scale, that is,having at least one cross-sectional dimension in the range from about0.1 μm to about 500 μm.

The term “microfluidic” means a system or device having channels orchambers that are on the micro-scale.

The term “monolithic polymer” means a polymerized polymerizableprecursor without a particulate filler.

The term “regulator” means any of various devices by which a fluid flowcan be started, stopped, or adjusted by a movable part that opens,shuts, or partially obstructs one or more openings.

The term “structural component” means a particle or a part affecting thestructure, composition, physical make-up, or nature of a substance.

The term “substrate” means a chip with lithographically fabricatedmicrochannels or conduits, and includes other conduit and channelnetworks such as capillaries and tubing.

The term “comprise” and variations of the term, such as “comprising” and“comprises,” are not intended to exclude other additives, components,integers or steps.

All dimensions specified in this disclosure are by way of example onlyand are not intended to be limiting. Further, the proportions shown inthese Figures are not necessarily to scale. As will be understood bythose with skill in the art with reference to this disclosure, theactual dimensions of any device or part of a device disclosed in thisdisclosure will be determined by intended use.

All amounts disclosed herein as a percentage is a weight percent of thetotal weight of the composition.

Referring now to FIG. 1A and 1B, there is schematically shown amicrofluidic control device 10 where the device is a composite checkvalve according to the present invention. The device comprises a conduit11 having a first end 12 and a second end 13. The conduit has a firstpath 14 and a second path 15 that are in fluid flow contact with theconduit 11. The device also has a regulator 16 that is moveable in theconduit 11. Referring now to FIG. 1B, and 1C, the regulator 16 has anouter dimension 17 that is larger than the first end 12 and the secondend 13 so the regulator 16 cannot pass out of the conduit 11. FIG. 1Cshows the cross-sectional configuration of the regulator 16 at positionA-A of FIG. 1B, which illustrates the outer dimension 17 of theregulator 16. The regulator 16 is comprised of a substantially elasticmaterial having a structural component which can be a composite polymerformed from a composite mixture comprising a polymerizable precursor anda particulate filler.

According to one embodiment of the present invention, as shown in FIG.1A and 1B, the regulator 16 is a composite check valve comprising aconduit 11 having walls fabricated in such a way that the shape of theconduit 11 encloses the regulator 16. The regulator 16 is movable in theconduit in a reciprocating, that is, a back and forth, or piston-likemotion. The motion of the regulator 16 is stopped by an altered conduitgeometry. The altered conduit geometry creates a barrier, also referredto herein as a weir, in the conduit 11 so that the regulator 16 cannotpass out of the conduit. In a preferred, but not required embodiment,the geometry of the conduit 11 is altered by changing the depth, width,diameter or shape of the conduit, or inserting another material betweenthe regulator 16 and the conduit 11, such as a porous membrane, thatallows fluid flow but prevents the regulator 16 from passing out of theconduit. In a most preferred but not required embodiment, the regulator16 is a sliding piece that is substantially cylindrically shaped movedby or moving against fluid pressure in a back and forth motion within acylindrically shaped conduit 11. The movement of the regulator 16 isstopped by narrowing the diameter of the conduit 11. However, otherregulator and conduit geometries can be used for stopping the motion ofthe regulator, as will be understood by those of skill in the art withreference to this disclosure.

The device 10 can additionally comprise an interconnecting conduit 18that provides a route for fluid to be redirected around the regulator 16when the regulator 16 is seated against the conduit second end 13, asshown in FIG. 1A. As shown in FIG. 1B, fluid does not pass through theconduit 11 when the regulator 16 is seated against the conduit first end12.

Referring now to FIG. 2A, 2B, 2C, and 2D, which schematically showmicrofluidic control devices according to the present invention, wherethe device is a composite check valve with an integrated flow path.According to this embodiment, a detached flow path 18, as shown in FIG.1A and 1B, is not needed for fluid flow. The device 30 comprises aconduit 31 having a first end 32 and a second end 33. The conduit has afirst path 34 that is in fluid flow contact with the conduit 31 and asecond path 35 that is in fluid flow contact with the conduit 31. Thedevice also has a regulator 36 that is moveable in the conduit. Theregulator has an outer diameter 37 that is larger than the first end 32and the second end 33 so the regulator 36 cannot pass out of the conduit31. The regulator 36 is comprised of a substantially elastic materialhaving a structural component. In a preferred but not requiredembodiment, the regulator 36 is a composite polymer obtained byphotoinitiated polymerization of a mixture of particulate filler and oneor more polymerizable precursors.

Referring again to FIG. 2A and 2B, FIG. 2A shows fluid flow into thedevice, which actuates the regulator 36 until the regulator 36 restsagainst the second end 33. A gap between the second end 33 and theregulator 36 allows unobstructed fluid flow between the first path 34,which is an inlet, and the second path 35, which is an outlet. FIG. 2Bshows the device stopping fluid flow in the opposite direction. Fluidentering from the second end 35 actuates the regulator 36 until itsrests against the first end 32. The fluid path is blocked and no flow isallowed from the second path 35 to the first path 34. Referring again toFIG. 2C and 2D, which schematically show an embodiment of the inventionwhere there is no conduit end directly between the second path 35 andthe regulator 36. According to this embodiment, the second end 33, whichis a side weir, provides the same functionality as the second end 33shown in FIG. 2A and 2B.

Referring now to FIG. 3A and 3B, a system comprising a plurality ofmicrofluidic control devices is schematically shown. In this system,multiple regulators are combined to create a system used for dispensingfluid from a sample source, that is, a sample dispenser. FIG. 3A and 3Bshow a system comprising a conduit 41, 42, and 43 where each conduit 41,42, and 43 has a first end 44, 45, and 46, respectively, and a secondend 47, 48, and 49, respectively. A first path 50, from a sample source,is in fluid flow contact with the conduit 41, 42, and 43, respectively.A second path 51, from a fluid source, is in fluid flow contact with theconduit 41 and 43, respectively. A flow path 55 is in fluid flow contactwith an actuation source. Each regulator 52, 53, and 54 is moveable inthe conduit 41, 42, and 43, respectively, and the outer diameter of eachregulator 52, 53, and 54 is larger than the first end 44, 45, and 46,respectively, and the second end 47, 48, and 49, respectively, so eachregulator cannot pass out of the respective conduit 41, 42, and 43.Further, each regulator 52, 53, and 54 is comprised of a substantiallyelastic material having a structural component. In a preferred but notrequired embodiment, the regulator 52, 53, and 54 is a composite polymerobtained by photoinitiated polymerization of a mixture of particulatefiller and one or more polymerizable precursors.

FIG. 3A shows the system 40 in a loading position, where sample inletcheck valve 401 is in an open position, that is, the regulator 52 isdrawn against the second end 47 of the conduit 41; in sample chamber 402the regulator 53 is a primary piston drawn against the second end 48 ofthe conduit 42, that is, the conduit closest to an actuation source; andoutlet check valve 403 is in the closed position, that is, the regulator54 is drawn against the first end 46 of the interconnected conduit 43.According to a preferred but not required embodiment, the sample sourcecan be a reservoir of a sample fluid, a system of channels containing asample fluid, or an external connection to the device containing asample fluid, such as a syringe. The actuation source is a source ofpressure and/or a vacuum used to actuate the primary piston. However,the system can have other configurations for loading and deliveringsamples and the sample source can be other fluid containing devices, aswill be understood by those of skill in the art with reference to thisdisclosure.

Now referring again to FIG. 3A and 3B, the system 40 additionallycomprises an excess fluid outlet 58 that can be a conduit leading to awaste reservoir, or can be a conduit connected to a vacuum source, or aconduit connected to the actuation source. In another embodiment, thesystem 40 additionally comprises interconnecting conduits to provide aroute to redirect fluid around the regulator 52 and 54. In anotherpreferred but not required embodiment, the device 50 additionallycomprises an analysis conduit 59, that is a conduit that can be open andfilled with material to connect a fluid, such as a running buffer fluidwith another apparatus, such as an analysis column. FIG. 3B shows thesystem 40 in an analysis position. In the analysis position, theregulator 52 in sample inlet check valve 401 is in a closed position,that is, drawn against the first end 44 of the interconnected conduit41; the regulator 53 in sample chamber 402 is drawn toward the first end45 of the conduit 42; and the regulator 54 in sample outlet check valve403 is in the closed position, that is, drawn against the second end 49of the interconnected conduit 43. According to the present invention,the system can have other regulator and conduit geometries the devicecan be used for procedures other than dispensing fluid from a samplesource, as will be understood by those of skill in the art withreference to this disclosure.

Now referring to FIG. 4A and 4B, a device for microfluidic control 60where the device is a mixing valve is shown. The device comprises aconduit 61 having a first end 62 and a second end 63. The conduit 61 hasa first path 64, a second path 65, and a third path in fluid flowcontact with the conduit 61. The device also comprises a regulator 67that is moveable in the conduit 61, where the regulator 67 has an outerdiameter that is larger than the first end 62 and the second end 63 sothe regulator 67 cannot pass out of the conduit 61. Further, theregulator 67 is comprised of a substantially elastic material having astructural component. In a preferred but not required embodiment, theregulator 67 is a composite polymer obtained by photoinitiatedpolymerization of a mixture of particulate filler and one or morepolymerizable precursors which can be a composite polymer formed from acomposite mixture comprising a polymerizable precursor and a particulatefiller.

Now referring again to FIG. 4A and 4B, in a preferred but not requiredembodiment, the device 60 is a mixing valve used for mixing fluids invarious concentrations, or to alternate the source of fluid flowing intoa conduit. As shown in FIG. 4A and 4B, the device 60 can be connected toan apparatus, such as an analysis column through flow path 66, and thedevice 60 can deliver a sample to the apparatus. As shown in FIG. 4A,fluid can flow from flow path 64, which is an inlet flow path to flowpath 66, which is an outlet flow path, when the regulator 67 is drawnagainst the second end 63. The regulator 67 can be drawn against thesecond end 63 when pressure greater than that in flow path 66 is appliedat flow path 64, or pressure at flow path 65 is reduced below that atflow path 64, or a combination thereof. As shown in FIG. 4B, fluid canflow from flow path 65 to flow path 66 when the regulator 67 is drawnagainst the first end 62. The regulator 67 can be drawn against thefirst end 62 when pressure greater than that in flow path 66 is appliedat flow path 65, or pressure at flow path 64 is reduced below that atflow path 65, or a combination thereof. In another preferred but notrequired embodiment, the pressure between flow path 64 and 65 can beswitched to alternately deliver different fluids from flow path 64 and65 into the flow path 66, which is an outlet flow path. Inherent fluiddispersion in the outlet flow path 66 can mix the fluids delivered fromflow path 64 and 65. The duration of the pressure pulses to flow path 64and 65 can be varied. For example, the-pressure pulse at flow path 64can be longer than the pressure pulse at flow path 65. Varying thepressure pulse of the flow paths will vary the relative volumes of fluidthat are individually delivered from flow path 64 and 65 to flow path66, and the fluids delivered to flow path 66 can be delivered in definedconcentrations. In another preferred but not required embodiment,multiple flow paths can be multiplexed to the outlet flow path 66 suchthat multiple inlet flow paths, greater than the two inlet flow paths 64and 65 shown in FIG. 4A and 4B, can be delivered to the outlet flow path66, and an alternately connected apparatus. According to the presentinvention, the device can have other regulator and conduit geometriesand the device can be used for procedures other than mixing fluids invarious concentrations, or alternating the source of fluid flowing intoa conduit, as will be understood by those of skill in the art withreference to this disclosure.

Now referring to FIG. 5A and 5B, a device 70 for microfluidic controlwhere the device has a substantially toothed shaped regulator, or agear, that is, a mechanism that performs a function in a machine, isshown. The device comprises a conduit 71 having a first end 72 and asecond end 73. The conduit 71 has a first path 74 and a second path 75in fluid flow contact with the conduit 71. The device also has aregulator 76 that is substantially toothed shaped and moveable in theconduit 71, and the regulator 76 has an outer diameter 77 that is largerthan the first end 72 and the second end 73 so the regulator 76 cannotpass out of the conduit 71. Further, the regulator 76 is comprised of asubstantially elastic material having a structural component. In apreferred but not required embodiment, the regulator 76 is a compositepolymer obtained by photoinitiated polymerization of a mixture ofparticulate filler and one or more polymerizable precursors. In anotherpreferred but not required embodiment, the substantially toothed shapedregulator 76 is rotationally moveable within the conduit. In a mostpreferred but not required embodiment, the device 70 additionallycomprises a substrate having an axle 78, also referred to herein as anaxis or center peg, and the regulator 76 is rotationally movable aroundthe axle. However, the regulator can have other gear configurations thatsurround a central point or pin, as will be understood by those of skillin the art with reference to this disclosure.

Now referring again to FIG. 5A and 5B, in a preferred but not requiredembodiment, the device can be used as a flowmeter. As shown in FIG. 5A,fluid can flow from the first path 74, which is an inlet path, to thesecond path 75, which is an outlet path, through the conduit 71. Whenthe fluid flows past the regulator 76, viscous drag from the fluid flowin the conduit can turn the regulator 76 at a rate that is a function ofthe fluid flow. A light source 79 can be used to measure the rotation ofthe regulator 76, which can be measured by examining the reflected (ortransmitted) light incident on a portion of the regulator 76 with adetector 80, such as a photo sensor. As shown in FIG. 5B, a mask 81 witha window 82 can be used to ensure that light is incident only on aregion where the teeth of the toothed wheel shaped regulator will bevisible. As the regulator 76 turns, and the teeth pass by the window 81,a measured signal of light reflected by the teeth will be periodic intime. In a preferred but not required embodiment, the device does notaliquot fixed volumes of fluid and the regulator can rotate freely in amoving fluid stream. As will be understood by those of skill in the artwith reference to this disclosure, the flow meter can operate with othertypes and arrangement of detectors, such as using a magnetic filler inthe regulator and sensing the motion of regulator 76 with a magneticsensor, for example as used in a Hall field sensor.

A second detector can be added to the device shown in FIG. 5A and 5B.The second detector can be located adjacent to the detector 80 and alonga path that parallels the direction of motion of regulator 76. In thisfashion, the two detectors are sequentially illuminated as the regulator76 rotates. In the illumination sequence, the signal from the firstdetector 80 changes prior to that from the second detector, or viceversa, providing the direction of rotation and hence the direction ofthe flow. As will be understood by those of skill in the art withreference to this disclosure, an increased flowrate resolution can beobtained through the addition of a second, a third, and more detectors.Also, a second, a third, and more sources of light can also be added tothe device. Additional detectors can be arranged along an arc that isparallel to the arc of rotation of regulator 76, and where the angularspacing of the detectors along this arc does not match the angle betweenthe teeth on regulator 76.

Now referring to FIG. 6, there is schematically shown a device formicrofluidic control 90 where the device has a plurality ofsubstantially toothed shaped regulators, also referred to as gears. In apreferred but not required embodiment, as shown in FIG. 6, the devicecomprises a conduit 91 having a first end 92 and a second end 93. Theconduit 91 has a first flow path 94 in fluid flow contact with theconduit 91, and a second flow path 95 in fluid flow contact with theconduit 91. The device also comprises a plurality of regulators 96 and97 that are moveable in the conduit 91, and the regulators 96 and 97each have an outer diameter 98 and 99, respectively, that is larger thanthe first end 92 and the second end 93 so each regulator 96 and 97cannot pass out of the conduit 91. Further, each regulator 96 and 97 iscomprised of a substantially elastic material having a structuralcomponent. In a preferred but not required embodiment, the regulator 96and 97 is a composite polymer obtained by photoinitiated polymerizationof a mixture of particulate filler and one or more polymerizableprecursors. In another preferred but not required embodiment, theregulators 96 and 97 are substantially toothed shaped and rotationallymoveable within the conduit. In a most preferred but not requiredembodiment, the device 90 additionally comprises a substrate having anaxle 100 and 101 and each regulator 96 and 97 is rotationally movablearound the axle 100 and 101. However, the regulator can have otherconfigurations and geometries that surround a central point or pin,including arbitrary geometries, as will be understood by those of skillin the art with reference to this disclosure.

Now referring again to FIG. 6, the device 90 can be used to performmechanical work. In a preferred but not required embodiment, fluid canflow from the first path 94, which is an inlet path, to the second path95, which is an outlet path, through the conduit 91, as shown in FIG. 9.When the fluid flows past the upper regulator 97, viscous drag from thefluid flow in the conduit can apply a force to the upper regulator 97,causing it to rotationally move about the axle 100. If more than onegear, such as the lower regulator 96, is meshed with the upper regulator97, it can actuate or be forced to rotate by the motion of the uppergear 97. However, the device 90 can be used for other procedures, aswill be understood by those of skill in the art with reference to thisdisclosure.

In one embodiment, the regulator is a substantially elastic materialhaving a structural additive or component structure. The regulator canbe a composite polymer formed from the polymerization of a compositemixture comprising a polymerizable precursor and a particulate filler.The regulator is movable in the conduit, that is, the regulator will notbond to the surrounding conduit walls or surrounding structures and isfree to move or rotate inside the conduit. The regulator is alsoconfined within regions of the conduit, as defined by specific featuresin the device geometry. In a preferred but not required embodiment, theregulator is formed by the in situ polymerization of the compositemixture in the conduit. In a more preferred but not required embodiment,the in situ polymerization is effected by light exposure or heating. Ina most preferred but not required embodiment, the composite mixture ispolymerized by the in situ photo-initiated and lithographically definedpolymerization of a polymerizable precursor and a particulate filler inthe conduit. According to this embodiment, the composite mixture ispolymerized in situ in the shape of a mask by exposing a region of theconduit to a radiating light through the mask. The use of a mask allowsfabrication of regulators with irregular and arbitrary geometry insidethe channel. Furthermore, since the regulators do not bond to thesurrounding conduit walls or surrounding structures, the regulators aremoveable in the conduit. For example, the regulator can move in a backand forth motion within the conduit, or the regulator can berotationally movable in the conduit. When the regulator is formed byphoto-initiated polymerization of the composite mixture in situ, opticalaccess to the composite mixture in the conduit region of polymerizationis provided. When the regulator is formed by in situ polymerization bythermal or other radiative means, optical access is not necessarilyprovided.

The composite mixture is comprised of one or more polymerizableprecursor and a particulate filler and can additionally comprise apolymerization initiator, such as a photo-initiator, and one or moresolvents. The composite mixture can be in the form of a slurry, that is,a liquid containing a particulate filler that may not necessarily besuspended, such as with a particulate filler having a particle size ofbetween about 100 nm and about 100 μm; a colloidal suspension, such aswith a particulate filler having a particle size range of between about1 nm and 100 nm); and a free-flowing liquid. However, the compositemixture can have other forms as will be understood by those of skill inthe art with reference to this disclosure.

The polymerizable precursor can be any of various monomer materials,such as butanediol diacrylate, diethylene glycol diacrylate, divinylbenzene, ethylene glycol diacrylate, hexanediol diacrylate, neopentylglycol diacrylate, pentaerythritol triacrylate, pentaerythritoltetracrylate, propylene glycol diacrylate, trimethylolpropanetriacrylate, heptafluorobutyl acrylate, trifluoroethylacrylate, andcombinations of the preceding monomers. In a preferred but not requiredembodiment, the polymerizable precursor is hexanediol diacrylate.However, other polymerizable precursors that are capable of forming acomposite polymer can be used according to the present invention, aswill be understood by those of skill in the art with reference to thisdisclosure.

The particulate filler can be in the form of a particle, bead, powder,fumed ceramic, fiber, floc, and other structural material, and acombination of the preceding particulate fillers. The particulate fillercan be encapsulated, that is, chemically non-bonded with the surroundingpolymer. Alternately, the particulate filler can bond directly to thesurrounding polymer. The size of the particulate filler is selected tobe less than the smallest dimension of the conduit and can be as smallas several nanometers. The composition of the particulate filler can bea glass, ceramic, metals and metal oxides, polymer, carbon black, andcombinations of the preceding fillers. The surfaces of the particulatecan be modified to control hydrophobicity, reactivity, etc., for examplean acrylate-modified. silica. In a preferred but not requiredembodiment, the particulate filler is selected from the group consistingof a silica, such as SiO₂, titania, such as TiO₂, alumina, such asAlO_(x), zirconia, such as ZrO_(x), magnetically permeable matearials,such as colloidal iron and iron-nickel alloys, mica, glass, andpolymers, such as polytetrafluoroethylene, poly(methyl methacrylate),latex, polystyrene, and combinations of the preceding fillers. In a morepreferred embodiment, the particulate filler is silica. However, otherforms, sizes, and compositions of the particulate fillers can be usedaccording to the present invention, as will be understood by those ofskill in the art with reference to this disclosure.

According to another embodiment of the present invention, a particulatefiller can be selected such that the composite polymer regulator issubstantially incompressible as compared to a monolithic polymerregulator. The particulate filler can occupy a substantial fraction ofthe volume of the regulator and the particulate filler can be selectedsuch that the particulate filler is selected to have a higher modulus ofelasticity than that of a monolithic polymer. According to the presentinvention, when the composite polymer regulator is under compression,the compaction of the regulator is limited to a value greater than thefiller volume fraction, thereby resulting in increased durability of theregulator under high compressive forces. In a preferred but not requiredembodiment, a composite polymer regulator will not exceed the bulkpolymer elastic limit of the polymer and the composite polymer regulatorwill be substantially resistant to creep when a compressive force isapplied to the composite polymer regulator. However, polymers with othercompressive properties can be used according to the present invention,as will be understood by those of skill in the art with reference tothis disclosure.

According to another embodiment, the particulate filler or otheradditives, such as dyes, etc., can be selected to add specific opticalproperties to a composite polymer regulator. Micro-scale polymer devicescan disappear when immersed in a liquid. The use of a particulate fillerin the composite mixture results in a composite polymer regulator thatcan exhibit amplified light scattering and/or light-absorbing and/orfluorescent properties as compared to a monolithic polymer. When aregulator with an optical property is desired, a particulate filler canbe selected that is naturally colored and/or that has a refractive indexsubstantially different than that of the bulk polymer and/or that isfluorescent. For example, light reflected, absorbed, or fluoresced froma regulator can be used as a diagnostic to obtain information on thelocation or orientation or motion of the regulator. Regulators havingoptical properties can be used in a sensing system, such as with amicrofluidic control device that is used as a flow meter. According tothe present invention, the particulate filler can be varied to modifyother properties of the composite polymer, such as the volume and typeof particulate filler can be varied to modify the friction coefficientof the regulator, and the volume and type of filler can be varied toimprove the polymerization resolution of the regulator, as will beunderstood by those of skill in the art with reference to thisdisclosure.

According to another embodiment of the present invention, a particulatefiller can be selected such that the composite polymer has asubstantially stable volume when exposed to various fluid compositions,that is, the composite polymer will have reduced or no dimensionalchange in response to variations in fluid composition, as compared to amonolithic polymer. Micro-scale polymer devices that are immersed inliquid can be prone to solvent-induced dimensional change due to thechemical interaction of the polymer surface with ions in the fluid, thatis, the shape and size of the polymer can change with exposure to fluidsof varying polarity. This behavior can limit the practical usefulness ofpolymer devices to perform reliable mechanical functions. According tothe present invention, an amount and a composition of a particulatefiller can be selected and added to the composite mixture, prior topolymerization, such that the composite polymer containing the selectedparticulate filler will have reduced or no dimensional change inresponse to variations in fluid composition. However, composite polymerswith other volumetric properties, such as other dimensional changeproperties, can be used according to the present invention, as will beunderstood by those of skill in the art with reference to thisdisclosure.

According to another embodiment of the present invention, a solvent canbe combined with the polymerizable precursor and the particulate filler.The solvent component can be any of various solvents capable of beingsuitably combined with the selected polymerizable precursor andparticulate filler, such as water and organic solvents. In a preferredbut not required embodiment, the solvent is selected from the groupconsisting of C₁-C₆ alcohols, C₄-C₈ ethers, C₃-C₆ esters, C₁-C₄carboxylic acids, methyl sulfoxide, sulfolane, and N-methyl pyrrolidone,and combinations of the preceding solvents. In a more preferred but notrequired embodiment, the solvent is methanol. However, other solventscan be used according to the present invention, as will be understood bythose of skill in the art with reference to this disclosure.

According to another embodiment of the present invention, a polymerizingelement can be combined with the polymerizable precursor and theparticulate filler. The polymerizing element can include any of variouscommon polymerization initiators and combinations thereof, such asazobisisobutyronitrile, azobisdihydrochloride, benzoyl peroxide, lauroylperoxide, potassium persulfate, and other common free radical thermal-and photo-initiators. In a preferred but not required embodiment, thepolymerizing element is a photo-initiator. In a more preferredembodiment, the polymerizing element is azobisisobutyronitrile. However,other polymerizing elements can be used according to the presentinvention, as will be understood by those of skill in the art withreference to this disclosure.

According to another embodiment of the present invention is a method ofmaking a device for microfluidic control. The method comprises combininga polymerizable precursor and a particulate filler to form a compositemixture. Then, the composite mixture is introduced into the conduit.Next, the conduit is exposed to an energy source to polymerize thecomposite mixture in situ, thereby forming a regulator, where theregulator is movable in the conduit, and the conduit is sized so theregulator cannot pass out of the conduit. In a preferred but notrequired embodiment, the composite mixture additionally comprises aphoto-initiator. In a more preferred but not required embodiment, theconduit is exposed to a radiating light source through a mask to formthe regulator.

Now referring to FIG. 7, which schematically shows a method of making adevice for microfluidic control according to the present invention. Asshown in FIG. 7, the method comprises selecting a substrate having aconduit 110. Then, a composite mixture 111 comprising a particulatefiller, a polymerizable precursor, a solvent and a photo-initiator arecombined and introduced into the conduit 110. The composite mixture 111can be combined by mixing together the liquid and particle componentsand may be in the form of a slurry, a colloidal suspension, or afree-flowing liquid. Next, a region of the conduit 110 containing thecomposite mixture 111 is selected. Next, the composite mixture isselectively polymerized and defined in the channel in a specificgeometry to form a composite polymer regulator 112 by exposing theconduit 110 to a radiating light 113, which can be ultraviolet light,heat, or other radiation, through an exposure mask 114. Next, theunpolymerized composite mixture 111 is removed from the conduit 110,such as by flushing the conduit 110, thereby forming a composite polymerregulator 112 that is movable in the conduit and sized so the regulator112 cannot pass out of the conduit 110.

In a preferred but not required embodiment, the method comprisespremixing the particulate filler and the polymerizable precursor to formthe composite mixture. In a more preferred but not required embodiment,the method additionally comprises forming the composite mixture bycombining the particulate filler with a premixed mixture of one or morepolymerizable precursors, photo-initiators, and solvents. However, thecomposite mixture can be combined by other methods, such as combiningthe composite mixture in situ, as will be understood by those of skillin the art with reference to this disclosure.

In another preferred but not required embodiment, the composite mixtureis introduced into a conduit that is an existing microchannel structureor a conduit formed within a substrate. In a more preferred embodiment,the composite mixture is introduced into a conduit by injecting thecomposite mixture into the conduit.

In a preferred but not required embodiment, the above-described methodsfor making a device for microfluidic control can be used to fabricate aregulator in a conduit where the conduit can be actuated by pressure. Inanother preferred embodiment, the above-described methods for making adevice for microfluidic control can be used to fabricate fluidiccomponents such as a valve and a flow meter inside a network ofmicrofluidic channels. The method of making a device for microfluidiccontrol can be used to fabricate composite polymer gears inside aconduit. This can be accomplished by fabricating a gear around a centerpoint, which can be a pin or axle formed in the substrate. However, theabove described methods for making a device for microfluidic control canbe used to fabricate other components for microfluidic control as willbe understood by those of skill in the art with reference to thisdisclosure.

In another embodiment, the present invention is a method formicrofluidic control. The method comprises selecting a device formicrofluidic control, where the device comprises a conduit having afirst path and a second path that are in fluid flow contact with theconduit, and a regulator, where the regulator is movable in the conduitand the conduit is sized so the regulator cannot pass out of theconduit. Then, fluid is placed into the conduit. Next, the regulator ismoved by the application of a pressurizing force to direct or stop thefluid flow.

In a preferred but not required embodiment, the fluid is placed in theconduit by injecting the fluid into the conduit. According to thepresent invention, the initial state of operation of the device is aload state. In the load state, a fluid fills an open conduit between thefirst path, which is a fluid inlet, and a second path, which is a fluidoutlet. The injection can be performed from this initial load state.However, the injection can be performed by other methods, such as withthe fluid inlet and fluid outlet at varying pressures, as will beunderstood by those of skill in the art with reference to thisdisclosure.

In another preferred but not required embodiment, the method comprises amethod for microfluidic control where the device delivers a sample to anapparatus, such as an analysis column. Now referring again to FIG. 3Aand 3B, the method comprises injecting a sample into the device when thedevice is in a load state. As shown in FIG. 3A, the regulator 53, whichis a primary piston, is drawn against the second end 48 of the conduit42 when the device is in the load state. Then, the sample is injectedinto the device through the flow path 50 at the first end 44 of theconduit 41. Next, the regulator 53 is actuated by applying a positivepressure, or a pressure that is greater than that of the adjoiningconduits through flow path 55, as shown in FIG. 3B. Next, the regulator53 is moved down the sample chamber 402 and an associated fluid flow andpressure are generated in front of the regulator 53 which moves theregulator 52 and closes is an inlet check valve 401, and also movesregulator 54 and opens outlet check valve 403, as shown in FIG. 3B.Next, the sample flows into an analysis column 59. The injection iscompleted when the regulator 53 reaches the first end 45 of the conduit56 at the end of the sample chamber 402. Any fluid from the actuationsource that continues to flow into the actuation inlet can be divertedto the excess fluid outlet 58 and an equilibrium pressure can be reachedbehind the primary piston that will be a function of the hydrodynamicflow resistance of the excess fluid outlet and ability of the actuationsource to deliver said pressure at that flow rate. The volume of sampleinjected into the analysis column can be approximately equal to theoriginal open volume in the sample chamber 402. The method of using thedevice to deliver a sample can be performed at other pressures,including vacuum, at the fluid outlet 58, the sample inlet, and in theanalysis column 59, that are of any value less than the pressure at theactuation source inlet.

In a preferred but not required embodiment, as shown in FIG. 3A, thedevice is in an inject state when the sample inlet, excess fluid outlet58, analysis column inlet 49, and outlet are at or near atmosphericpressure, and the regulator 53 is drawn against the second end 48 of theconduit 42. Applying a negative pressure differential (vacuum) to thesecond end 48 of the conduit 42 through actuation inlet 55 draws theregulator 53, which is a primary piston, toward the actuation inlet 55.The inlet check valve 401 is opened by generating a corresponding fluidflow and vacuum behind the primary piston 53, which opens the inletcheck valve 401 and also closes the outlet check valve 403. A samplefluid is drawn from plow path 50 through the first end 44 of the conduit41, which is a sample inlet, and an open conduit path is created betweenthe sample inlet and an excess fluid outlet 58, as shown in FIG. 3A.Additional suction can be applied to the excess fluid outlet 58 to flushthe sample chamber 402 with multiple volumes of sample in order toensure the sample chamber 402 contains pure sample fluid. This step canalso be performed with a separate cleaning/flushing fluid in the samplereservoir in order to clean the device prior to insertion of a newsample fluid. In an alternate embodiment, the excess fluid outlet 58 andflow path to the actuation inlet 56 can be connected to achieve the sameeffect. The sample inlet, analysis column inlets and outlets can be atvarious pressures above the actuation inlet/excess fluid outlet pressurein order to achieve this process.

In another embodiment, the pressure in the analysis column 59 can be thehighest pressure in the system at that time, leading to the outlet checkvalve 403 closing immediately after the injection state is terminated.This procedure leads to an alternate method of filling the samplechamber and achieving the load state. Now referring again to FIG. 3A and3B, when the actuation inlet and excess fluid outlet are at or nearatmospheric pressure and the pressure in the analysis column is abovethe sample inlet pressure, the regulator 53, which is a primary piston,is in an ‘inject’ state, where the regulator is drawn against the firstend 45 of the conduit 42. Applying a positive pressure differential tothe sample inlet forces the inlet check valve 401 to open and theregulator 53 moves toward the actuation inlet 56. The outlet check valve403 remains closed due to the higher pressure in the analysis column 59.The sample fluid flows through the opened conduit path 41 and fills thesample chamber 402. When the primary piston reaches the second end 48 ofthe conduit 42, as shown in FIG. 4, the sample fluid flows through thesample chamber and out the excess fluid outlet. The excess fluid outletcan be connected to the second end 48 of the conduit 42 in thisembodiment.

Now referring to FIG. 11, which is a flow chart showing the method ofusing a device according to the present invention as a flowmeter. Asshown in FIG. 11, the method comprises selecting a device having asubstantially toothed wheel regulator, according to the presentinvention. Then, a fluid with a viscosity is passed by the regulator,thereby turning the regulator at a fluid flow rate. Next, a radiatinglight is directed to a toothed portion of the regulator and theradiating light is reflected or transmitted to a detector, such as aphoto-sensor. Next, the reflected or transmitted light is measured as aperiodic signal in time. Next, the signal is processed and the frequencyof the signal is determined and related to the fluid flow rate as afunction of the fluid viscosity. In one embodiment, multiple regulatorsof varying dimensions and conduit cross-sections can be used insuccession to widen the dynamic range of the measurement and improvemeasurement accuracy.

EXAMPLE I Composite Mixture

A composite mixture was formed from the substances listed in Table I.TABLE I SUBSTANCE AMOUNT ethoxylated trimethylolpropane triacrylate 900μL trifluoroethylacrylate (2,2,2 TFEA) 100 μL2,2′-azobisisobutyronitrile  5 mg Dioxane 500 μL 500 μL of2-methoxyethanol 500 μL silica particles  10%

The composite mixture was prepared by mixing the ethoxylatedtrimethylolpropane triacrylate, SR454, available from SartomerCorporation, Exton, Pa., US and the trifluoroethylacrylate, 2,2,2 TFEA,available from Sigma-Aldrich Corp., St. Louis, Mo., US to form a monomermixture. Then, the photo-initiator, 2,2′-azobisisobutyronitrile, AIBN,(5 mg) available from Sigma-Aldrich Corp., St. Louis, Mo., US was addedto the monomer mixture. A solvent mixture was prepared by combining thedioxane, available from Sigma-Aldrich Corp., St. Louis, Mo., US and the2-methoxyethanol, available from Sigma-Aldrich Corp., St. Louis, Mo., USThe monomer mixture and solvent mixture were then mixed in a 8:2volume:volume ratio, that is, 800 μL of the monomer mixture was mixedwith 200 μL of the solvent mixture. A particulate filler of 1 μmdiameter, non-porous silica particles (10 wt %), available fromSigma-Aldrich Corp., St. Louis, Mo., US, was then added to the monomermixture and solvent mixture to create a suspension/slurry of monomer,solvent, and particles.

EXAMPLE II Incompressibility Of Composite Polymers

A particulate filler was selected such that the composite polymerregulator was substantially incompressible, as compared to a monolithicpolymer regulator. As a comparative example, a regulator comprising amonolithic polymer was substantially extruded through a fine passagewhen the regulator was subjected to a 10,000 psi high compressive force.Whereas, a regulator comprising a composite polymer containing a 50%silica particulate filler, prepared according to the present invention,compressed to about 50% of the initial volume. This degree ofcompression did not exceed the bulk polymer elastic limit of the polymerand the regulator part was substantially resistant to extrusion.

As a further example, the compressive strength of Nylon 6,6 and comparedto the compressive strength of a composite polymer prepared with Nylon6,6 according to the present invention. The compressive strength ofNylon 6,6 was tested and at 10% compression, the compressive strengthwas about 12,000 psi. Whereas, a composite polymer prepared according tothe present invention with 30% glass-filled Nylon 6,6 was tested and thecompressive strength at 10% compression was about 39,000 psi.

EXAMPLE III Volume Stability Of Composite Polymers

A particulate filler was selected such that the composite polymer had asubstantially stable volume when exposed to various fluid compositions,that is, the composite polymer had reduced or no dimensional change inresponse to variations in fluid composition, as compared to a monolithicpolymer. As a comparative example, a monomer mixture containingethoxylated trimethylolpropane triacrylate and trifluoroethylacrylate inan 80:20 volume:volume ratio was mixed with methoxyethanol in a 50:50volume:volume ratio. Trace amounts of azobisisobutyronitrile, aphotoinitiator, was added and the mixture was photopolymerized. When theresulting monolithic polymer was placed in water, the element shrank to55% of its original volume. Whereas, following the same procedure, andadding 7 wt % of particles of colloidal antimony pentoxide, with anouter diameter of 7-11 nm, to the mixture, the polymerized compositepolymer shrank by only 20% of its original volume.

EXAMPLE IV Microfluidic Control Device

A regulator that was used as a composite piston was formed byintroducing the composite mixture from Example I into a 150 μm innerdiameter optically transparent silica capillary by injecting thecomposite mixture into the capillary with a syringe. A 2 mm length ofthe capillary was then exposed to broadband ultraviolet radiation,peaking at around 365 nm with total energy flux of 40 mW/cm², for 30seconds. Upon exposure to the ultraviolet radiation, a compositeparticle-filled solid polymer piston with a length dimension of 2 mm anda width dimension that is approximately equal to the inner diameter ofthe surrounding capillary was formed. The composite piston did not bondto the surrounding capillary and was thus free floating. The piston wasmobilized by applying between about 1 psi to about 5 psi of pressure toone terminal end of this first capillary. An adjoining second capillary,having a 25 μm inner diameter, was connected to the second terminal ofthe first capillary. The composite piston within the first capillary waspushed against the adjoining capillary and put under pressure in excessof 2000 psi with little to no damage or permanent distortion to thecomposite piston. Ejecting the composite piston from the first capillaryand examining the composite piston under a microscope confirmed thegeometry of the composite piston. The composite piston was iterativelyexposed to acetonitrile, methanol, isopropanol, water, and aqueousbuffers with pH ranging from between about 2 to about 12. The swellingand shrinking of the composite piston was observed between exposures tothese liquids and the swelling and shrinking of the composite piston wasless than 10% of its original diameter in all cases.

Although the present invention has been discussed in considerable detailwith reference to certain preferred embodiments, other embodiments arepossible. Therefore, the scope of the appended claims should not belimited to the description of preferred embodiments contained herein.

1. A device for microfluidic control comprising: a) a conduit having afirst end and a second end; b) a first path in fluid flow contact withthe conduit; c) a second path in fluid flow contact with the conduit;and d) a regulator that is moveable in the conduit, wherein theregulator has an outer dimension that is larger than the first end andthe second end so the regulator cannot pass out of the conduit; and theregulator comprises a substantially elastic material having a structuralcomponent.
 2. A device according to claim 1 wherein the regulator issubstantially incompressible.
 3. A device according to claim 1 whereinthe regulator has an optical property.
 4. A device according to claim 1wherein the regulator has a substantially stable volume when exposed toa fluid.
 5. A device according to claim 1 wherein the inner dimension ofthe conduit is less than about 1 millimeter.
 6. A device according toclaim 1 wherein the regulator is substantially cylindrically shaped andmoveable in a back and forth motion within the conduit.
 7. A deviceaccording to claim 1 wherein the regulator is substantially toothedwheel shaped and rotationally moveable within the conduit.
 8. A devicefor microfluidic control comprising: a) a conduit having a first end anda second end; b) a first path in fluid flow contact with the conduit; c)a second path in fluid flow contact with the conduit; and d) a regulatorthat is movable in the conduit, wherein the regulator has an outerdimension that is larger than the first end and the second end so theregulator cannot pass out of the conduit; and the regulator is acomposite polymer formed from a composite mixture comprising apolymerizable precursor and a particulate filler.
 9. A device accordingto claim 8 wherein the composite mixture additionally comprises aphoto-initiator.
 10. A device according to claim 8 wherein the compositemixture comprises two or more polymerizable precursors and a particulatefiller.
 11. A device according to claim 8 wherein the outer dimension ofthe particulate filler is less than about 1 micrometer.
 12. A device formicrofluidic control comprising: a) a conduit having a first end and asecond end; b) a first path in fluid flow contact with the conduit; c) asecond path in fluid flow contact with the conduit; d) a third path influid flow contact with the conduit; and e) a regulator that is moveablein the conduit, wherein each regulator has an outer diameter that islarger than the first end and the second end so each regulator cannotpass out of the conduit; and each regulator comprises a substantiallyelastic material having a structural component.
 13. A device formicrofluidic control comprising: a) a conduit having a first end and asecond end; b) a first path in fluid flow contact with the first end ofthe conduit; c) a second path in fluid flow contact with the second endof the conduit; and d) a plurality of regulators that are moveable inthe conduit, wherein each regulator has an outer diameter that is largerthan the first and second flow paths so the regulators cannot pass outof the conduit; and each regulator is a substantially elastic materialhaving a structural component.
 14. A device for microfluidic controlcomprising: a) a substrate; b) a conduit in the substrate having a firstend and a second end; c) a first path in fluid flow contact with thefirst end of the conduit; d) a second path in fluid flow contact withthe second end of the conduit; and e) a regulator movable in theconduit, wherein the regulator has an outer diameter that is larger thanthe first and second flow paths so the regulator cannot pass out of theconduit; and the regulator is a substantially elastic material having astructural component.
 15. A device according to claim 14 wherein theparticulate filler is sized to be no more than 50% of the size of thesmallest flow path in the conduit.
 16. A device according to claim 14wherein the substrate additionally comprises an axle, and wherein theregulator is substantially toothed wheel shaped and rotationallymoveable around the axle.
 17. A device for microfluidic controlcomprising: a) a conduit having a first end and a second end; b) a firstpath in fluid flow contact with the first end of the conduit; c) asecond path in fluid flow contact with the second end of the conduit;and d) a regulator that is moveable in the conduit, wherein theregulator has an outer diameter that is larger than the first and secondflow paths so the regulator cannot pass out of the conduit; and theregulator is formed in the conduit by the in situ polymerization of acomposite mixture.
 18. A device according to claim 17 wherein theregulator is formed in the conduit by the in situ polymerization of thecomposite mixture with an energy source.
 19. A device according to claim17 wherein the composite mixture comprises a polymerizable precursor, aparticulate filler, and a photo-initiator and the regulator is formed inthe conduit by the in situ polymerization of the composite mixture witha radiating light source.
 20. A system for microfluidic controlcomprising: a) a plurality of conduits, each conduit having a first endand a second end; b) a first path in fluid flow contact with one or moreconduit; c) a second path in fluid flow contact with one or moreconduit; and d) a plurality of regulators, each regulator beingindependently moveable in a separate conduit, wherein each regulator hasan outer diameter that is larger than the first end and the second endso each regulator cannot pass out of the conduit; and each regulatorcomprises a substantially elastic material having a structuralcomponent.
 21. A method of making a device for microfluidic controlcomprising: a) combining a polymerizable precursor and a particulatefiller to form a composite mixture; b) introducing the composite mixtureinto a conduit; and c) exposing the conduit to an energy source topolymerize the composite mixture in situ thereby forming a regulator,wherein the regulator is movable in the conduit, and the conduit issized so the regulator cannot pass out of the conduit.
 22. A methodaccording to claim 21 wherein the composite mixture additionallycomprises a photo-initiator and wherein the energy source is a radiatinglight source and the conduit is exposed to the radiating light sourcethrough a mask to form the regulator.
 23. A method of making a devicefor microfluidic control comprising: a) selecting a substrate having aplurality of conduits; b) combining a polymerizable precursor and aparticulate filler to form a composite mixture; c) introducing thecomposite mixture into each conduit; and d) exposing each conduit to anenergy source to polymerize the composite mixture in situ therebyforming a plurality of regulators, wherein each regulator is movable ina conduit and each conduit is sized so the regulator cannot pass out ofthe conduit.
 24. A method according to claim 23 additionally comprisingremoving unpolymerized composite mixture from a conduit.
 25. A method ofmaking a device according to claim 23 wherein the substrate has three ormore conduits, and the composite mixture is introduced into three ormore conduits to form three or more regulators on the same substrate.26. A method of making device according to claim 23 wherein the energysource is a radiating light source and one or more conduits is exposedto the radiating light source to form one or more substantiallycylindrically shaped regulators, and each substantially cylindricallyshaped regulator is moveable in a back and forth motion within theconduit.
 27. A method of making a device according to claim 23 whereinthe energy source is a radiating light source and one or more conduitsis exposed to the radiating light source to form one or moresubstantially toothed wheel shaped regulators, and each substantiallytoothed wheel shaped regulator is rotationally moveable within theconduit.
 28. A method of making a device according to claim 23 whereinthe device comprises two or more conduits and two or more regulators andthe energy source is a radiating light source and each conduit isexposed to the radiating light source to form a regulator within eachconduit.
 29. A method of making a device according to claim 23 whereinthe substrate has an axle, and the conduit is exposed to a radiatinglight to form a substantially toothed wheel shaped regulator around theaxle.
 30. A method for determining a fluid flow rate in a microfluidicdevice comprising: a) selecting a device for microfluidic control, thedevice having one or more regulators that are moveable in the conduit,b) moving a fluid with a viscosity past a regulator, thereby moving oneor more regulators at a fluid flow rate; c) directing a radiating lightto a portion of one or more regulators such that the radiating light isreflected or transmitted to a detector; d) measuring the reflected ortransmitted light as a periodic signal in time; and e) processing thesignal; f) determining the frequency of the signal and relating thesignal frequency to the fluid flow rate.
 31. A method according to claim30 wherein the radiating light is reflected or transmitted to aplurality of detectors.
 32. A method according to claim 30 wherein aplurality of radiating lights are directed to a regulator and theradiating lights are reflected or transmitted to a plurality ofdetectors.
 33. A method according to claim 30 wherein at least one ofthe regulators is a substantially toothed wheel shaped regulator and theradiating light is directed to a toothed portion of the regulator suchthat the radiating light is reflected or transmitted to a detector.